Transcription factor c-Myb: novel prognostic factor in osteosarcoma

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Authors

ŘÍHOVÁ Kamila DÚCKA Monika STANICZKOVÁ ZAMBO Iva VYMĚTALOVÁ Ladislava ŠRÁMEK Martin TRČKA Filip VERNER Jan DRÁPELA Stanislav FEDR Radek SUCHÁNKOVÁ Tereza PAVLATOVSKÁ Barbora ONDROUŠKOVÁ Eva KUBELKOVÁ Irena ZAPLETALOVÁ Danica TUČEK Štěpán MÚDRY Peter ADÁMKOVÁ KRÁKOROVÁ Dagmar KNOPFOVÁ Lucia ŠMARDA Jan SOUČEK Karel BORSIG Lubor BENEŠ Petr

Year of publication 2022
Type Article in Periodical
Magazine / Source Clinical & Experimental Metastasis
MU Faculty or unit

Faculty of Science

Citation
Web https://link.springer.com/article/10.1007%2Fs10585-021-10145-4
Doi http://dx.doi.org/10.1007/s10585-021-10145-4
Keywords c-Myb; Chemoresistance; Metastasis; Osteosarcoma; Prognosis; Proliferation
Description The transcription factor c-Myb is an oncoprotein promoting cell proliferation and survival when aberrantly activated/expressed, thus contributing to malignant transformation. Overexpression of c-Myb has been found in leukemias, breast, colon and adenoid cystic carcinoma. Recent studies revealed its expression also in osteosarcoma cell lines and suggested its functional importance during bone development. However, the relevance of c-Myb in control of osteosarcoma progression remains unknown. A retrospective clinical study was carried out to assess a relationship between c-Myb expression in archival osteosarcoma tissues and prognosis in a cohort of high-grade osteosarcoma patients. In addition, MYB was depleted in metastatic osteosarcoma cell lines SAOS-2 LM5 and 143B and their growth, chemosensitivity, migration and metastatic activity were determined. Immunohistochemical analysis revealed that high c-Myb expression was significantly associated with poor overall survival in the cohort and metastatic progression in young patients. Increased level of c-Myb was detected in metastatic osteosarcoma cell lines and its depletion suppressed their growth, colony-forming capacity, migration and chemoresistance in vitro in a cell line-dependent manner. MYB knock-out resulted in reduced metastatic activity of both SAOS-2 LM5 and 143B cell lines in immunodeficient mice. Transcriptomic analysis revealed the c-Myb-driven functional programs enriched for genes involved in the regulation of cell growth, stress response, cell adhesion and cell differentiation/morphogenesis. Wnt signaling pathway was identified as c-Myb target in osteosarcoma cells. Taken together, we identified c-Myb as a negative prognostic factor in osteosarcoma and showed its involvement in the regulation of osteosarcoma cell growth, chemosensitivity, migration and metastatic activity.
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